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Rhythm and blues: fly’s heart beats to the pulse of a blue laser

It’s called optogenetics and it refers to the use of light to regulate cells. With it, bioengineers are now able to create research animals such as fruit flies or mice that carry genes for proteins sensitive to light. The researchers can turn those proteins on and off with a laser in the live animal to study how manipulating those proteins affects function of organs, such as the heart or brain.

In this case, NIBIB-funded researchers engineered fruit flies that carry light-sensitive proteins in their hearts. When hit by a blue laser, the proteins open channels that cause a flow of ions or charged particles that cause the heart to beat.

The heart can be optically stimulated in the fruit fly larva, pupa, and adult. Credit: Chao Zhou, Lehigh University.

The heart beats with each flash of a blue laser that passes through the skin of the insect—an exoskeleton called a cuticle. They used the system to regulate the heart rate of adult flies and fly larva and pupa to introduce a completely non-invasive “optical pacemaker”. The hope is that the experimental system can eventually be used to develop potential therapies for human heart disease including cardiac arrest and arrhythmias.

The study was headed by senior author, Chao Zhou, Ph.D., Department of Electrical and Computer Engineering at Lehigh University in Bethlehem, Pennsylvania and was reported in the October issue of Science Advances.1

Before optogenetics, scientists used electrical stimulation to alter heart rhythms in experimental animals—an approach that takes advantage of the fact that the heart naturally beats in response to electrical signals. However, experimental electrical stimulation has a number of drawbacks including the need for invasive placement of electrodes, lack of specificity to only the heart tissue, and potential to cause tissue damage.

“The choice of the fruit fly makes this work particularly interesting and ingenious,” explains Richard Conroy, Ph.D., Director of the NIBIB Division of Applied Science and Technology, “because they are able to study how changes in the beating pattern of the heart can impact development of the whole organism—something that could not be done in a mouse, for example.”

Optogenetic pacemaker: Researchers used laser light to regulate the heartbeat of a fruit fly.

Indeed the studies done in mice involved surgically opening the chest wall to expose the heart to light or implanting optic fibers in the mice so the light is guided to the organ to be light-stimulated such as the heart or brain. Both procedures are significantly more invasive compared to the ease of stimulating the heart of a fruit fly. Once the gene that produces the light sensitive protein, which is only made in the heart, was introduced into the fruit flies, the researchers were able to use the pulsing blue laser to manipulate the heart throughout fruit fly development. The laser was used to control the heart rate of the fruit fly larva, and the next stage, known as the pupa, as well as in adults.

In each developmental stage the heart beats at different speeds and has differing characteristics, which was recently reported by the same group in PLOS One.2 One of the most striking is found in the pupa where the heart rate is reduced significantly, with the heart completely stopping on the second day of the pupa stage and then starting back up a day later, where it steadily increases to reach the maximum heart rate in the adult. Differences in each developmental stage gave the researchers the opportunity to test the ability of the optogenetic system to influence and ultimately control the varying heart rates at each stage.

“Working with fruit flies adds the powerful tool of designing studies that span the life cycle,” explains Zhou. “Because we can alter the heart rate in the pupa non-invasively it allows us to study the effect of early heart irregularities on the development of the adult fly. This provides great potential for experiments aimed at understanding developmental abnormalities such as arrhythmias and to pursue new therapeutic strategies that may eventually be applied to human cardiac disorders.”

The research was supported by funding from the National Institutes of Health through the National Institute of Biomedical Imaging and Bioengineering grants EB010071 and EB019704, the National Institute of Arthritis and Musculoskeletal and Skin Diseases grant AR063271, the National Institute of Aging grant AG014713, and the National Institute of Mental Health grant MH060009. Funding was also provided by the National Science Foundation, the Cure Alzheimer’s Fund, the Massachusetts General Hospital, and the Lehigh University Start-Up-Fund.